LYSIS OF RAT-BRAIN MICROVASCULAR ENDOTHELIAL-CELLS MEDIATED BY RESTING BUT NOT ACTIVATED MBP-SPECIFIC CD4(+) T-CELL LINES

Previous work from this laboratory showed that the encephalitogenic potential of myelin basic protein (MBP)-specific T cells is inseparably associated with their cytotoxic potential. MBP-specific T cells lyse all cells that present autoimmunogenic MBP peptide in context of appropriate MHC class II determinants. Beside class II-induced glia cells, blood-brain barrier-derived endothelial cells were identified as highly susceptible target cells for cytotoxic MBP-specific T cells. Here we show that the cytotoxic reaction against endothelial cells essentially differs from cytotoxicity against other target cells. In contrast to classical T cell-mediated lytic responses, which are most efficiently executed by activated T cells, rat brain endothelium (RBE) lysis could only be mediated by resting T cells. Activated MBP-specific T cell blasts were not able to mediate strong RBE lysis. Furthermore, T cell lines with specificities for protein antigens other than MBP did not cause RBE lysis. A role of the cytolytic capacity of resting MBP-specific T cells in the pathogenesis of experimental autoimmune encephalomyelitis is probable.